NEW
GENE NECESSARY FOR PLANT GROWTH AND DEVELOPMENT DISCOVERED USING A PROMISING
EXPERIMENTAL TECHNIQUE

By taking a fresh approach to an old problem,
University of California, San Diego biologists and colleagues at other
institutions have found a new gene essential for plant growth, a discovery
that could lead to the design of better herbicides and even novelty plants.

Despite 100 years of research on auxin, a plant hormone
essential in regulating plants’ development and responses to their
surroundings, including the ability of plants to grow toward light, much
remains unknown about how auxin is synthesized and how it works. A new
approach known as “chemical genetics,” in which chemicals
are used to regulate activities of proteins produced by specific genes,
has revealed a previously unknown gene, SIR1, which functions
to keep the effects of auxin in check. The UCSD scientists say that one
implication of their discovery is the potential development of environmentally
safe herbicides from chemicals that impede the action of auxin by over-activating
the SIR1 gene.

A paper featured on the cover of the October 10, 2003 issue
of Plant Physiology details the chemical genetic approach. The
discovery of the SIR1 gene was reported in the August 22nd issue
of Science.

“By using chemical genetics we have been able to identify
a new gene that regulates the important plant hormone auxin,” explains
Yunde Zhao, assistant professor of biology at UCSD, who was largely responsible
for the work. “This finding can be applied to manipulating plant
growth, including the development of a new generation of herbicides. Chemical
genetics shows a great deal of promise for helping us understand aspects
of plant biology, like how auxin is synthesized and controlled, where
genetic methods used by researchers until now only had limited success.”

Interestingly, the researchers found that if, at different
times, they applied and withdrew the chemical that inactivated the SIR1
protein, this led to strangely shaped plants because SIR1 usually dampens
the effect of auxin. Auxin plays important roles in the development of
roots, stems and leaves, but either too much or too little auxin interferes
with development. Zhao thinks this could have implications for the design
of novel flowers and other plant structures.

“Some had leaves that developed into striking trumpet-like
shapes,” he says.

Chemical genetics has two major advantages over the genetic
approaches traditionally used. First, chemical genetics can permit a researcher
to study the effects of more subtle gene changes than eliminating a gene.
This is important because a gene may play more than one role, at multiple
times during development. If the gene has an essential role early in development,
then eliminating it will kill the organism, preventing researchers from
discovering other roles for that gene later in development. Since chemical
genetics is reversible, by simply stopping the application of a chemical
that inactivates or activates a protein produced by a gene, it can be
used to study what a gene does at different stages in development.

A second advantage of chemical genetics has to do with the
fact that the molecules used can often inactivate related proteins with
the same function. A problem with the traditional approach of eliminating
a particular gene to determine its function is that if there are two or
more genes with the same or similar functions, removing one of those genes
may have no apparent effect on the health of the organism. This gene redundancy
is more common in plants than in animals.

“About 70% of the genes in the model plant we used
in our study, Arabidopsis, may have at least two copies,”
Zhao points out. “This is a problem with traditional genetic approaches,
but with chemical genetics a small molecule will most likely be able to
inactivate all members of a closely related family of proteins provided
that they operate by a similar mechanism.”

Both gene redundancy and the lethal effect of eliminating
genes essential for plant development have plagued biologists studying
auxin for many years. Because chemical genetics can be useful in solving
these two problems, Zhao thinks that the application of chemical genetics
will likely lead to rapid advances in the field.

While the technique of chemical genetics had been used by
researchers working on yeast, bacteria and mammalian cells in culture,
its application in plant biology is still at an infancy stage. Zhao cites
his background as a biochemist as helping him to come with a fresh perspective
to the auxin problem.

“When I started working on plants, I didn’t
have much knowledge in plant biology,” Zhao says. “So I wasn’t
afraid of taking on those projects the plant biologists didn’t think
would work.”

The SIR1 work was initiated by Zhao in the laboratory
of Joanne Chory, a Howard Hughes Medical Institute investigator at the
Salk Institute for Biological Studies, and continued in Zhao’s own
lab at UCSD in collaboration with Xinhua Dai, research associate in biology
at UCSD; Helen Blackwell, now assistant professor of chemistry at University
of Wisconsin, Madison; and Stuart Schreiber, professor of chemistry at
Harvard University and an HHMI investigator. The work was supported by
the National Institutes of Health and the Howard Hughes Medical Institute.
The Plant Physiology paper on chemical genetic approaches to
plant biology was written in collaboration with Helen Blackwell, with
support from the NIH.